Detailed analysis of variants in FTO in association with body composition in a cohort of 70-year-olds suggests a weakened effect among elderly
| Autor: | Lilia A. Hedberg, Markus Sällman Almén, Helgi B. Schiöth, Tomas Axelsson, Lars Johansson, Joel Kullberg, Christian Benedict, Josefin A. Jacobsson, Karl Michaëlsson, Robert Fredriksson, Håkan Ahlström, Samantha J. Brooks, Lars Lind |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Candidate gene lcsh:Medicine Disease Linkage Disequilibrium Diagnostic Radiology Cohort Studies Glucose homeostasis lcsh:Science Genetics Multidisciplinary Anthropometry Magnetic Resonance Imaging Phenotype Alpha-Ketoglutarate-Dependent Dioxygenase FTO Body Composition Regression Analysis Medicine Female Radiology Research Article Genetic Markers Clinical Research Design Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Childhood obesity medicine Humans Obesity Genetic Association Studies Genetic association Aged Nutrition lcsh:R Proteins Computational Biology nutritional and metabolic diseases Human Genetics medicine.disease Cross-Sectional Studies Haplotypes Genetic Polymorphism lcsh:Q Energy Intake Population Genetics |
| Zdroj: | PLoS ONE, Vol 6, Iss 5, p e20158 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Obesity is a complex and a highly individualized disease and the molecular mechanisms behind this disorder need to be better elucidated. Identification of genes and genetic variants that are involved provide opportunities to establish a genetic understanding of the disease. These findings may also provide more rational approaches to therapy, either by identifying underlying causes or point out the need for different treatments. In addition, the timing and severity of obesity may provide insights into the aetiology of obesity and also identify age-specific determinants of weight gain. Recently, genome-wide association studies have led to a rapid progress in our understanding of the genetic basis of various diseases and candidate genes for obesity have been identified. The overall aim of this thesis was to investigate the genetic impact on severity of childhood obesity and the associations between obesity and genetic variants in the fat mass and obesity associated gene, FTO, and MGAT1, the gene encoding mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetyl-glucosaminyltransferase. We show that the impact of parental body mass index (BMI) on the severity of obesity in children is strengthened as the child grows older, whereas the age at obesity onset is of limited importance. By association studies, we show that single nucleotide polymorphisms downstream MGAT1 influence susceptibility to obesity. Moreover, these variants affect the levels of unsaturated fatty acids and desaturase indices, variables previously shown to correlate with obesity. Furthermore, one variant in the first intronic region of FTO is associated with obesity among children but not with BMI or other measures of adiposity at older ages. However, this variant shows a weight-dependent association with cognitive function among elderly men. By direct sequencing, we identified novel variants in FTO, affecting glucose homeostasis in a BMI-independent manner. Furthermore, we found gender specific effects for FTO, both regarding obesity susceptibility and related phenotypes. |
| Databáze: | OpenAIRE |
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